{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T18:30:43Z","timestamp":1794508243114,"version":"4.9.1"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,2,23]],"date-time":"2027-02-23T00:00:00Z","timestamp":1803340800000},"content-version":"am","delay-in-days":328,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK128612"],"award-info":[{"award-number":["R01 DK128612"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.ejmech.2026.118694","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T16:51:19Z","timestamp":1771433479000},"page":"118694","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Structure-activity relationship profiling of N-substituted 8-trifluoromethyl-9H-purin-6-amines as mitochondrial protonophores"],"prefix":"10.1016","volume":"308","author":[{"given":"Emily L.","family":"Krinos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei J.","family":"Fields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella M.","family":"DeLuca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Foutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan R.","family":"Hargett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Beretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riya","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reilly K.","family":"Gwinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances L.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle L.","family":"Hoehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-8548","authenticated-orcid":false,"given":"Webster L.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ejmech.2026.118694_bib1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cell.2005.02.001","article-title":"Mitochondria, oxidants, and aging","volume":"120","author":"Balaban","year":"2005","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.ejmech.2026.118694_bib2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41392-025-02253-4","article-title":"Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances","volume":"10","author":"Xu","year":"2025","journal-title":"Signal Transduct. Targeted Ther."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118694_bib3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11010-022-04496-z","article-title":"Oxidative stress in metabolic diseases: current scenario and therapeutic relevance","volume":"478","author":"Raut","year":"2023","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.ejmech.2026.118694_bib4","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/7934442","article-title":"Targeting oxidative stress mechanisms to treat lzheimer's and Parkinson's Disease: a critical review","volume":"2022","author":"Aborode","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"9","key":"10.1016\/j.ejmech.2026.118694_bib5","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118694_bib6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s40005-020-00481-0","article-title":"Mitochondrial targeted strategies and their application for cancer and other diseases treatment","volume":"50","author":"Li","year":"2020","journal-title":"J. Pharm. Investig."},{"issue":"12","key":"10.1016\/j.ejmech.2026.118694_bib7","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.bbabio.2011.09.018","article-title":"Chemiosmotic coupling in oxidative and photosynthetic phosphorylation","volume":"1807","author":"Mitchell","year":"2011","journal-title":"BBA - Bioenergetics"},{"issue":"4784","key":"10.1016\/j.ejmech.2026.118694_bib8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/191144a0","article-title":"Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism","volume":"191","author":"Mitchell","year":"1961","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.ejmech.2026.118694_bib9","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nrm1592","article-title":"The mitochondrial uncoupling-protein homologues","volume":"6","author":"Krauss","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ejmech.2026.118694_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155672","article-title":"Mitochondrial UCP1: potential thermogenic mechanistic switch for the treatment of obesity and neurodegenerative diseases using natural and epigenetic drug candidates","volume":"130","author":"Reyad-ul-Ferdous","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.ejmech.2026.118694_bib11","doi-asserted-by":"crossref","DOI":"10.2337\/diabetes.53.2007.S130","article-title":"The biology of mitochondrial uncoupling proteins","volume":"53","author":"Rousset","year":"2004","journal-title":"Diabetes"},{"issue":"4","key":"10.1016\/j.ejmech.2026.118694_bib12","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.freeradbiomed.2010.05.010","article-title":"Uncoupling protein-3 lowers reactive oxygen species production in isolated mitochondria","volume":"49","author":"Toime","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.ejmech.2026.118694_bib13","first-page":"1","article-title":"Mitochondrial uncoupling proteins and","volume":"6","author":"Busiello","year":"2015","journal-title":"energy metabolism"},{"issue":"8","key":"10.1016\/j.ejmech.2026.118694_bib14","doi-asserted-by":"crossref","DOI":"10.3390\/cells8080795","article-title":"Mitochondrial uncoupling: a key controller of biological processes in physiology and diseases","volume":"8","author":"Demine","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.ejmech.2026.118694_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2021.100941","article-title":"Uncoupling proteins in the mitochondrial defense against oxidative stress","volume":"83","author":"Hass","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.ejmech.2026.118694_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.112656","article-title":"Uncoupling proteins as a therapeutic target for the development of new era drugs against neurodegenerative disorder","volume":"147","author":"Kumar","year":"2022","journal-title":"Biomed. Pharmacother."},{"issue":"9","key":"10.1016\/j.ejmech.2026.118694_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.drudis.2023.103717","article-title":"UCP1 activation: hottest target in the thermogenesis pathway to treat obesity using molecules of synthetic and natural origin","volume":"28","author":"Jagtap","year":"2023","journal-title":"Drug Discov. Today"},{"issue":"5","key":"10.1016\/j.ejmech.2026.118694_bib18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1124\/molpharm.123.000704","article-title":"Thermogenic modulation of adipose depots: a perspective on possible therapeutic intervention with early cardiorenal complications of Metabolic Impairment","volume":"104","author":"El-Yazbi","year":"2023","journal-title":"Mol. Pharmacol."},{"issue":"8","key":"10.1016\/j.ejmech.2026.118694_bib19","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1038\/s42255-025-01311-z","article-title":"A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss","volume":"7","author":"Cal","year":"2025","journal-title":"Nat. Metab."},{"issue":"8","key":"10.1016\/j.ejmech.2026.118694_bib20","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1021\/acs.chemrestox.8b00132","article-title":"Development of a decision tree for mitochondrial dysfunction: uncoupling of oxidative phosphorylation","volume":"31","author":"Enoch","year":"2018","journal-title":"Chem. Res. Toxicol."},{"issue":"21","key":"10.1016\/j.ejmech.2026.118694_bib21","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1016\/j.jmb.2018.03.025","article-title":"Use the protonmotive force : mitochondrial uncoupling and reactive oxygen species","volume":"430","author":"Berry","year":"2018","journal-title":"J. Mol. Biol."},{"issue":"11","key":"10.1016\/j.ejmech.2026.118694_bib22","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1021\/acs.jmedchem.7b01182","article-title":"Small molecule mitochondrial uncouplers and their therapeutic potential","volume":"61","author":"Childress","year":"2018","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118694_bib23","doi-asserted-by":"crossref","DOI":"10.3390\/cells8030280","article-title":"2,4 dinitrophenol as medicine","volume":"8","author":"Geisler","year":"2019","journal-title":"Cells"},{"issue":"3","key":"10.1016\/j.ejmech.2026.118694_bib24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s13181-011-0162-6","article-title":"2,4-Dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death","volume":"7","author":"Grundlingh","year":"2011","journal-title":"J. Med. Toxicol."},{"issue":"1-3","key":"10.1016\/j.ejmech.2026.118694_bib25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0378-4274(99)00193-9","article-title":"Effects of neutral ionophores on membrane electrical characteristics of NG108-15 cells","volume":"114","author":"Doebler","year":"2000","journal-title":"Toxicol. Lett."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118694_bib26","first-page":"106","article-title":"2,4-Dinitrophenol: \u2018diet\u2019 drug death following major trauma","volume":"9","author":"Freeman","year":"2021","journal-title":"Anesthe. Rep"},{"issue":"43","key":"10.1016\/j.ejmech.2026.118694_bib27","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.2307\/4575357","article-title":"A study of the munitions intoxications in France","volume":"34","author":"Roger","year":"1919","journal-title":"Publ. Health Rep."},{"key":"10.1016\/j.ejmech.2026.118694_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2025.102204","article-title":"Diverse actions of 15 structurally unrelated mitochondrial uncouplers in cells and mice","volume":"99","author":"Shah","year":"2025","journal-title":"Mol. Metabol."},{"issue":"7","key":"10.1016\/j.ejmech.2026.118694_bib29","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/2211-5463.13817","article-title":"Structural investigations on the mitochondrial uncouplers niclosamide and FCCP","volume":"14","author":"Ng","year":"2024","journal-title":"FEBS Open Bio"},{"issue":"12","key":"10.1016\/j.ejmech.2026.118694_bib32","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/S2468-1253(23)00198-X","article-title":"Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial","volume":"8","author":"Noureddin","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"issue":"2","key":"10.1016\/j.ejmech.2026.118694_bib33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41419-017-0092-6","article-title":"Effect of mitochondrial uncouplers niclosamide ethanolamine (NEN) and oxyclozanide on hepatic metastasis of colon cancer","volume":"9","author":"Alasadi","year":"2018","journal-title":"Cell Death Dis."},{"issue":"11","key":"10.1016\/j.ejmech.2026.118694_bib34","article-title":"Niclosamide ethanolamine \u2013 induced mild mitochondrial uncoupling improves diabetic symptoms in mice","volume":"20","author":"Tao","year":"2014"},{"issue":"26","key":"10.1016\/j.ejmech.2026.118694_bib35","doi-asserted-by":"crossref","first-page":"16980","DOI":"10.1021\/acsomega.1c01993","article-title":"New approach to drug discovery of a safe mitochondrial uncoupler: OPC-163493","volume":"6","author":"Okamoto","year":"2021","journal-title":"ACS Omega"},{"issue":"2","key":"10.1016\/j.ejmech.2026.118694_bib36","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.molmet.2013.11.005","article-title":"Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane","volume":"3","author":"Kenwood","year":"2014","journal-title":"Mol. Metabol."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118694_bib37","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-16298-2","article-title":"Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice","volume":"11","author":"Alexopoulos","year":"2020","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.ejmech.2026.118694_bib38","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.molmet.2013.11.005","article-title":"Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane","volume":"3","author":"Kenwood","year":"2014","journal-title":"Mol. Metabol."},{"key":"10.1016\/j.ejmech.2026.118694_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1252141","article-title":"BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases","volume":"14","author":"Xiong","year":"2023","journal-title":"Front. Endocrinol."},{"issue":"10","key":"10.1016\/j.ejmech.2026.118694_bib40","doi-asserted-by":"crossref","DOI":"10.1111\/apha.14217","article-title":"Beneficial effects of MGL-3196 and BAM15 combination in a mouse model of fatty liver disease","volume":"240","author":"Zhou","year":"2024","journal-title":"Acta Physiol."},{"issue":"7","key":"10.1016\/j.ejmech.2026.118694_bib41","doi-asserted-by":"crossref","DOI":"10.1172\/JCI152401","article-title":"BAM15 treats mouse sepsis and kidney injury, linking mortality, mitochondrial DNA, tubule damage, and neutrophils","volume":"133","author":"Tsuji","year":"2023","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.ejmech.2026.118694_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2022.128912","article-title":"Conversion of oxadiazolo[3,4-b]pyrazines to imidazo[4,5-b]pyrazines via a tandem reduction-cyclization sequence generates new mitochondrial uncouplers","volume":"73","author":"Dai","year":"2022","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118694_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116916","article-title":"Design, synthesis, and biological evaluation of imidazo[4,5-b]pyridine mitochondrial uncouplers for the treatment of metabolic dysfunction-associated steatohepatitis (MASH)","volume":"280","author":"Salamoun","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118694_bib44","series-title":"Analysis and Interpretation of Microplate-based Oxygen Consumption and Ph Data","author":"Divakaruni","year":"2014"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342600139X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342600139X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T21:10:29Z","timestamp":1779743429000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342600139X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":42,"alternative-id":["S022352342600139X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118694","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-activity relationship profiling of N-substituted 8-trifluoromethyl-9H-purin-6-amines as mitochondrial protonophores","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118694","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118694"}}